Journal of Natural Pr&s Vol. 57, No. 5, pp. 670-672, May 1994
670
4-QUINOLINONE, 2-QUINOLINONE, '+ACRIDANONE, AM) FUROQUINOLINE ALKALOIDS FROM THE AERIAL PARTS OF BORONZA BOWMANZI MONIRAMAN, ALEXANDER I. GRAY,PETERG. WATER~~AN,*
Phytorhernistty Research Luhatwies, Department of Pharmaceutical Sciences, University dStratbcly&, Gkasgmu, GI I X W , UK and JAMES A. ARMSTRONG' Westem Australian Herbarium, Department of Consewation and Land Management, Como, Western Australia, Australia 6052
bmm.-Thirteen alkaloids have been isolated from the aerial parts of Bwonia bowmrrnii (Rutaceae). These were identified on the basis of spectroscopic analysis as l-acetoxyrnethyl-2,3dimethyl-4-quinolinone, l-acetoxymethyl-2-methyl-4-quinolinone,2,3-dimethyl-4quinolinone, l-acetoxymethyl-2-nonyl-4quinolinone [4], l-methyl-2-nonyl-4quinolinone, 2-nonyl-4quinolinone, l-hydroxy-9-acridanone, 1,Bdihydroxy-9-acridanone, 1,Bdihydroxy3-methoxy-9-acridanone [lo], preskimmianine, dictamnine, evolitrine, and y-fagarine. Alkaloids 4 and 10 are novel.
In a recent paper (1)we reported the occurrence of a number of novel 4quinolinone and acridone alkaloids from Boronia lanceolata F. Muell. (Rutaceae), a species found in Northern Australia. Several of the quinolinone alkaloids had an unusual N-acetoxymethyl substituent that had previously been reported from Boronia temata Endl. (2), a species found in southwestern Australia and at that point the only other recorded source of alkaloids in the genus. Continuing our studies on Boronia we have now undertaken an examination of a sample of B. boMMniiF.Muell.,whichoccursinnortheastern Australia (3). This species, which had not previously been investigated, has also been found to be a good source of 4quinolinone and, to a lesser extent, acridone and furoquinoline alkaloids. The petroleum ether extract of B. bowmanii afforded thirteen alkaloids, six 4-quinolinones E1-61, a ~quinolinone 13,three9-acridanones{%lo},and three furoquinolines 111-131. Of these 1, 2, 3,8, and 9 had previously been isolated
'Current Address: Department of Conservation and Land Management, Hackett Drive, Crawley, Perth, Western Australia, Australia 6009.
Rl 1 2
3 4 5 6
R,
R2 Me Me Me n-nonyl n-nonyl n-nonyl
CH,OAc CH,OAc
H CH,OAc Me
H
Me0
H 7
8 9
10
Rl
R2
H H OMe
H OH OH
R, Me
H Me
H H H
Ahsan et al.: Alkaloids from Boronia
May 19941
67 1
13
R,
R, Rl
R*
11 12
H H
H
13
OMe
H
OMe
from B. lanceolata (l), and their identity was established by co-tlc and comparison of uv and 'H-nmr data with values already published. Compounds 5 (4,5), 6 ( 5 ) , 7 (6), 11 (7), 12 (8),and 13 ( 7 3 ) were identified by comparison with literature data. The hreims o f 4 revealed the molecular ion at mlz 343 (C,,H&JO,>. The 'Hnmr spectrum (Table 1) was similar to that ofthe known compound 2,revealing four aromatic proton multiplets comprising an ABCD system, an isolated aromatic proton and methylene and acetoxyl resonances typical of an N-acetoxymethyl moiety. Additional signals for a deshielded methylene, seven further methylenes, and a methyl suggested an nnonyl substituent, comparable to that found in 5 and 6 (4,5). AJ-modulated TABLE 1.
'H and 13C-NmrChemical Shift Data for Compound 4.'
Position
...... ...... ...... ...... ...... ...... 8 ...... 9 ...... 10 . . . . . 1'. . . . . . 2'. . . . . . 3'. ..... l"4"...
2 3 4 5 6 7
s".... . .
6.20 s 8.38 dd (8.0, 1.5) 7.36 dd (8.0, 7.2) 7.64 ddd (8.6, 7.2, 1.5) 7.49 d (8.6) 6.13 s 2.12 s 2.74 t (7.6) 1.67 rn 1.261.46m 0.87 t (6.8)
154.4 112.0 178.5 126.9 124.1 132.6 115.5
141.4 126.4 68.9 170.1 20.9 22.8-33.6 14.2
'Spectra run in CDCI,, and] values are shown in
parentheses.
C-nmr spectrum (Table 1) was in agreement with that expected for 4. The hreims of 10 displayed a base peak at mlz 257, corresponding to the molecular formula Cl4Hl1NO4.The 'Hnmr spectrum (Table 2) revealed five aromatic protons, two ofwhich exhibited only meta- coupling and could be attributed to H-2 and H-4. The three remaining aromatic protons were in an ABC spin-system suggesting placement at H5, H-6, and H-7. Other signals were a 3H singlet, which could be due to either an 0-methyl or an N-methyl substituent and two chelated OH resonances. TheJmodulated 13C-nmrspectrum (Table 2) confirmed the presence of a methoxyl group. These data allowed the identification of 10 as 1,8-dihydroxy-3-methoxy9-acridanone. TABLE 2.
Position 1
'Hand I3C-NrnrChemical Shift Data for Compound 10.'
I
......
2 ...... 3 ......
4 ...... 5 ......
...... ...... ...... ...... 10 . . . . . 11 . . . . . 12 . . . . .
6 7 8 9
13 . . . . . 14 _ . . _ . OMe . . .
6, 13.44 sa (OH) 6.54 d (2.2)
6.48 d (2.2) 6.% d (8.4) 7.52 dd (8.4, 8.0) 6.81 d (8.0) 13.34 sa (OH)
I
6, 167.2 96.3 164.5 90.3 106.6 136.6 107.6 162.8 185.1
13.02 brs 144.9 104.6 108.8
3.69 s
'Assigknents within a column able; spectra were run in pyridine-d,.
143.3 56.0
k interchange-
The alkaloid profile exhibited by B. bowmanii is very similar to that of B. lanceolata (1). 4-Quinolinone alkaloids with the unusual N-acetoxymethyl substituent have now been identified in all three Bwonia species from which alkaloids have been isolated. Otherwise this substituent is known from only two other sources in the Rutaceae, Eriostemon australasius ssp. banksii (9), which is itself closely allied to Bwonia (lo), and in
67 2
Journal of Natural Products
Zanthxyhn (11).A further striking rnetabolic convergence is the co-occurrence of these 2-aLkyl-4quinolinones and simple acridones in the Eurasian species Ruta gramlens (4,12).
EXPERIMENTAL GENERAL EXPERIMENT& PROCEDURES.-UV (Perkin-Elmer 552) in MeOH; ir (Perkin-Elmer 781) KBr disks; specific rotations (Perkin-Elmer 241); nmr Bruker AMX-400 ('H, 400 MHz; ',C, 100.6 MHz), all pulse sequences used modified Bruker microprograms; eims AEI-MS902 doublefocusing at 70 eV. Melting points (uncorrected), Reichert hot stage. Petroleum ether refers to the bp 60-80' fraction. F"T hiATERIhL.-Boronia bmumanii was collected from Cape York Peninsula, in the far north of Queensland, Australia, and a voucher specimen has been deposited at the Western Australian Herbarium, Perth (PERTH 01734091).
EXTRACTION AND ISOLATION.--The ground aerial parts (280 g) were extracted sequentially in a Soxhlet with petroleum ether, EtOAc, and MeOH. The concentrated petroleum ether extract was fractionated by vlc over Si gel eluting with petroleum ether containing increasing amounts of EtOAc. Elution with 5 0 4 0 % EtOAc yielded a mixture of 8 , 9 , and 10.These were purified by cc using Sephadex LH-20 to give 8 12 mg, mp 255'; lit. (1) 252-2540]. Compounds 9 and 10 were separated by prep. tlc on Si gel, with multiple development using CHC1, to give 9 14.5 mg, mp 252"; lit. (1) 2507 and 10 (2 mg). Elution with 7 0 4 0 % EtOAcgave11{1.4mg,mp 132";lit.(4) 129-1320], 12 (3 mg, mp 114'; lit. (13) 11411507,13(1.5 mg,mp 140°;lit.(14) 141-1427, 4 (35 mg), and 7 ( 2 mg, mp 154"; lit. (6) 1511520], which were also separated by cc over Sephadex and then prep. tlc on Si gel [multiple development with toluene-EtOAc (17:3)]. Elution with EtOAc alone yielded 1 150 mg, mp 174'; lit. (1) 175-1787. Vlc of the EtOAc extract over Si gel afforded, on elution with 5-20% MeOH in EtOAc, a rnixture of alkaloids. On concentration of the eluate 3 {lo0 mg, mp 314-317"; lit. (1) 310-3157 crystallized out. Passage of the supernatant through a Sephadex LH-20 column followed by prep. tlc over Si gel [solvent: CHC1,-MeOH (98:2) multipledevelopment)gave2{1 mg,mp 162'; lit.(l) 160-164'1, 5 f 1 5 mg,mp75';lit. (5)74-760]and 6 145 mg, mp 135"; lit. (15) 138-1390]. 1-Aceto~thyl-2-nonyl-4-qttinolinae[41.Amorphous solid, mp 79"; uv A max (log E) 234 (4.13), 313 (3.82), 326 (3.87) nm;ir Y rnax 2920, 2840,1740,1630,1600,1585,1485,1470,1420, 1380,1300,1245,1210,1200,1150,1075,1020,
mol. 57, No. 5
955,845,760 cm-'; 'Hand I3C nmr see Table 1; eims m/z M* 343.2134 (calcd for C , , H a O , , 343.2147) ( 6 3 , 329 (15), 314 ( 2 4 , 300 (70), 298 ( l l ) , 286 (19), 284 (53), 270 (23), 258 (18), 244 (71), 231 (87), 214 (lo), 202 ( l l ) , 198 ( l l ) , 188 (78), 186 (21), 184 (19), 172 (54), 159 (1001, 144 (9), 132 (8), 130 (21), 77 (10). 1,8-Dibydroxy-3 -metboxy-9-acridanone [lo].-Yellow needles from CHCl,, mp 275"; uv A max (log E) 253 (4.35), 271 (4.23), 306 (3.81), 311 (3.83), 325 (3.60), 397 (3.40) MI; ir u max 3300, 1665, 1645, 1605, 1490, 1355, 1285, 1235,1200,1160,1110,825,760 cm-'; 'Hand 13C nmr see Table 2; eims mlz M' 257.0691 (calcd for C,,H,,NO,, 257.0688) (loo), 228 ( 5 4 , 214 (11), 199 (16), 186 (15), 140 (lo), 128 (6), 114 (15), 95 (13). ACKNOWLEDGMENTS One of us (M.A.) thanks the Association of Commonwealth Universities for the award of a Fellowship.Wearemost grateful to JohnClarkson for the collection of plant material. Nmr studies were performed in the Nmr Laboratory of the University of Strathclyde. LITERATURE CITED 1. 2. 3.
4. 5.
6. 7. 8.
9.
10. 11. 12. 13. 14.
15.
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Received 7 Dam& 1993
